Project title: New ACE2 activator and its prodrug as novel therapeutic reagents for inflammatory pulmonary diseases. Pneumonia and associated inflammatory lung diseases (ILD) are a leading cause of death among children and elderly worldwide and a significant source of morbidity and mortality among hospitalized patients. Interestingly, the diseases are associate with over-activation of the renin-angiotensin system and impaired ACE2 activity. The overall goal of present study will validate the therapeutic benefits of a newly discovered class of ACE2 activators, named H4, in bacterial pneumonia associated inflammatory lung disease. The immediate objectives of this application are: 1) To explore the mechanisms by which H4 and its prodrugs buffer RAS over-activity; 2) To evaluate the efficacy of and strategies for H4 and its prodrugs to reverse the development of bacterial pneumonia by limiting neutrophilic lung inflammation. This project is highly significant because ILD are associated with many infectious and non-infectious lung diseases, in which, many of them are projected to remain the leading cause of death. Therefore, not only our research will lead to the validation of a new therapy but we will assess the impact of that treatment for inflammatory lung diseases. These studies will make a significant pre-clinical insight of a novel ACE2 activator, h4 and its pro- drug in preventing and treating inflammatory lung diseases.